CA-3 lecture on Anemia and Transfusion

1. The Transfusion Trigger:
When Should You
Give Red Cells?
Harriet W. Hopf, MD
Professor of Anesthesiology
University of Utah

2. Goals
 To understand
 the effect of anemia on oxygen transport
 mechanisms that compensate for anemia
 the risks of transfusion
 the concept of a transfusion trigger

3. Objective
 Participants will be able persuasively to
defend their decision to transfuse / not to
transfuse red cells

4. Why Transfuse Red Cells?

5. Why Transfuse Red Cells?
 To maintain O2 delivery to organs
 To prevent inadequate O2 consumption

6. How Do We Measure Need?
 Ideal
 Tissue oxygen
 Good-- but not practical
 O2ER (VO2/DO2)
 Madjdpour and Spahn. BJA 2005; 95:33-42
 Real
 Hemoglobin
 Hemodynamics

7. Physiologic Effects of Anemia
 Why is there a wide range of “normal” and
“acceptable” hemoglobin?

8. Physiologic Effects of Anemia
 Compensate by increased cardiac output
 CO = HR X SV
 HR increases 4 bpm / g Hb
 SV increases as well
 Increased contractility (active)
 Decreased SVR (passive)
 Increased venous return (passive)
Weiskopf et al. Transfusion 2003; 43: 235-40

9. Physiologic Effects of Anemia
 Under anesthesia, no HR increase
 Increased CO is from increased SV
Majdpour and Spahn. BJA 2005; 95:33-42.

10. Fick’s Principle

11. Fick’s Principle
 CO = VO2 / AVDO2
 AVDO2 = CaO2-CvO2
 CO2 = SO2(HbX1.34) + PO2(0.003)
 mL O2 / dL blood

12. Does Dissolved Oxygen Matter?

13. Hemoglobin bound oxygen
Hb (g/dL)
14 10 7 3
PaO2 (mmHg)
CaO2 18.76 13.40 9.38 4.02
100
18.76 13.40 9.38 4.02
500
18.76 13.40 9.38 4.02
2000

14. Dissolved Oxygen
Hb (g/dL)
14 10 7 3
PaO2 (mmHg)
CaO2 0.30 0.30 0.30 0.30
100
1.50 1.50 1.50 1.50
500
6.00 6.00 6.00 6.00
2000

15. Putting it all together
Hb (g/dL)
14 10 7 3
PaO2 (mmHg)
CaO2 18.76 13.40 9.38 4.02
0.30 0.30 0.30 0.30
100 19.06 13.70 9.68 4.32
18.76 13.40 9.38 4.02
1.50 1.50 1.50 1.50
500 20.26 14.90 10.88 5.52
18.76 13.40 9.38 4.02
6.00 6.00 6.00 6.00
2000 24.76 19.40 15.38 10.02

16. Does Dissolved Oxygen Matter?

17. What if you can’t transfuse?

18. What if you can’t transfuse?
 Administer 100% oxygen
 Equivalent to 1-1.5 g/dL Hb
 1 g Hb fully saturated = 1.34 mL O2
 PaO2 500 mm Hg = 1.5 mL O2
 PaO2 300 mm Hg = 0.9 mL O2
Weiskopf et al. Anesthesiology, 96(4), 871-7, 2002.

19. Dissolved Oxygen Matters!!!
Hb (g/dL)
14 10 7 3
PaO2 (mmHg)
CaO2 18.76 13.40 9.38 4.02
0.30 0.30 0.30 0.30
100 19.06 13.70 9.68 4.32
18.76 13.40 9.38 4.02
1.50 1.50 1.50 1.50
500 20.26 14.90 10.88 5.52
18.76 13.40 9.38 4.02
6.00 6.00 6.00 6.00
2000 24.76 19.40 15.38 10.02

20. What Happens to AVDO2?
 Normal AVDO2 using Fick’s Equation
 Hb 14 g/dL
 CO 50 dL / min (5 Lpm)
 VO2 250 mL O2 / min
 AVDO2 = 250/50 = 5
 CaO2 19 mL O2/dL blood
 CvO2 14 mL O2/dL blood
 p50 CvO2 = 7

21. What if AVDO2 Doesn’t Change?
Hb (g/dL)
14 10
PaO2 (mmHg)
CaO2 18.76 13.40 13.7 - 5 = 8.7
0.30 0.30
100 19.06 13.70 Close enough to 7!!!

22. What Happens to AVDO2?
 Assume CO can increase
 Hb 7 g/dL
 CO 100 dL / min (10 Lpm)
 VO2 250 mL O2 / min
 AVDO2 = 250/100 = 2.5

23. What if AVDO2 Does Change?
Hb (g/dL)
14 10 7
PaO2 (mmHg)
CaO2 18.76 13.40 9.38
0.30 0.30 0.30
100 19.06 13.70 9.68
CvO2
14.06 8.70 4.68
AVDO2 = 5
CvO2
16.56 11.20 7.18
AVDO2 = 2.5

24. What if you can’t transfuse?
 Maximize CaO2
 FiO2 1.0
 Hyperbaric oxygen (intermittent)
 Minimize VO2
 Intubate
 Paralyze
 Sedate
 Cool (?) to 35.5C

25. What if you can’t transfuse?
 Maximize CO
 Volume
 Goal is isovolemia
 Consider TEE guidance
 Don’t measure Hb!
 Don’t use dopamine
 Increased VO2 mostly cardiac

26. Dissolved Oxygen Matters!!!
Hb (g/dL)
14 10 7 3
PaO2 (mmHg)
CaO2 18.76 13.40 9.38 4.02
0.30 0.30 0.30 0.30
100 19.06 13.70 9.68 4.32
18.76 13.40 9.38 4.02
1.50 1.50 1.50 1.50
500 20.26 14.90 10.88 5.52
18.76 13.40 9.38 4.02
6.00 6.00 6.00 6.00
2000 24.76 19.40 15.38 10.02

27. Risks of Transfusion
 Infection
 HIV 1: 500K-1500K
 HBV 1:30K-200K
 HCV 1: 2000K-3000K
 Bacterial 1:28K-43K
 Malaria 1:4000K
 vCJD Recent reports
Majdpour and Spahn. BJA 2005; 95:33-42.

28. Risks of Transfusion
 Transfusion Reaction 1:13K
 Mistransfusion 1:14K-18K
 TRALI 1:5K-529K
 Expensive
 Limited supply
Majdpour and Spahn. BJA 2005; 95:33-42.

29. Risks of Transfusion
 Cancer recurrence
 Surgical site infection
 Mortality
 Role for leucoreduction?
 Old vs. new blood?
 Koch et al, NEJM 358:1229, 2008
 Weiskopf et al, Anesth. 104:911, 2006
Majdpour and Spahn. BJA 2005; 95:33-42.

30. Transfusion Guidelines
 Are there guidelines?
 ASA Guidelines, Anesth 105:198-208, 2006.
 Are they based on data?
 “strongly agree” transfuse < 6 g/dL
 “strongly agree” don’t transfuse >10g/dL
 How good are physicians at following them?

31. Joint Commission
 Patient Blood Management Performance Measures Project
 Transfusion Consent
 RBC Transfusion Indication
 Plasma Transfusion Indication
 Platelet Transfusion Indication
 Blood Administration Indication
 Preoperative Anemia Screen
 Preoperative Blood Type / Antibody Screen
http://www.jointcommission.org/patient_blood_management_performance_measures_project/

32. Transfusion Trigger
 Really a TARGET not a TRIGGER
 Healthy patient
 7 g / dL
 Cardiopulmonary disease
 10 g / dL (?8-9)
 Prevent tachycardia

33. What does this mean?
 Healthy patient, Hb 14 g/dL
 Assume 500 mL (1 unit) whole blood loss = 1
g/dL Hb decrease
 Assume volume replaced
 EBL >3500 mL before consider transfusion

34. How low can you go?
 Unmedicated, healthy volunteers at rest
 Hb 5 g / dL
 No VO2-DO2 dependency
 Fatigued
 Mild cognitive impairment
 Slightly slower and less accurate
 Still in normal range
 Reversed by RBC transfusion at Hb 7 g/dL
 Reversed by 100% O2 via NRB
Weiskopf et al. Anesthesiology, 96(4), 871-7, 2002.

35. What about surgical patients?
 Anemia increases 30-day mortality, CV
complications, and LOS
 Non-cardiac surgery
 Polycythemia similar effects
 Wu et al. JAMA 297:2481, 2007 (98% men)
 Colorectal surgery
 ~50% women but not analyzed separately
 Leichtle et al, J Am Coll Surg 212:187, 20011
 Cardiac surgery
 Koch et al, Crit Care Med 34:1608, 2008

36. How Should We Manage Anemia?
 Is anemia a marker for disease or inherently
causative?
 Preoperative treatment:
 2 weeks oral iron (200 mg) reduces transfusion
 9.4 vs 27.4%, p<0.05
 Okuyama et alSurg Today 35:36, 2005
 ESA reduces transfusion, increases DVT
 Laupacis and Fergusson, Transfus Med 8:309, 1998

37. How Should We Manage Anemia?
 Is anemia a marker for disease or inherently
causative?
 Risk-adjusted, propensity-matched
 ≥4 U blood predicts increases:
 Mortality
 Infection
 LOS
 Dunne et al, J Surg Res 102:237, 2002

38. Critical Care Transfusion RCT
 838 patients, Hb <9 g/dL, within 72 h of
admit
 Trigger <7 Target 7-9
 Trigger <10 Target 10-12
Hebert et al. NEJM, 1999; 340:409-17.

39. Critical Care Transfusion RCT
Trigger
<7 g / dL <10 g/dL P value
30d Mortality
Overall 18.7 23.3 0.11
APACHE II
8.7 16.1 0.03
<21
Age <55 yr 5.7 13 0.02
CV Disease 20.5 22.9 0.69

40. Table 3. Unadjusted Rates of Outcomes and Adjusted Results of Cox Regression Predicting 30-Day
Death and Death or Recurrent Myocardial Infarction Using Transfusion as a Time-Dependent
Covariate.
HCT 25% best cut-off for transfusion
Rao, S. V. et al. JAMA 2004;292:1555-1562
Copyright restrictions may apply.

41. Individualize
 Transfusion target (7 vs. 10 vs. 8…)
 Acute vs. chronic anemia
 Rate of bleeding
 Hemodynamics
 What about ADLs?
 Should target differ in men and women?

42. Summary
 Transfusions of RBC can be life-saving
 Also cause serious morbidity and mortality
 Individualize therapy
 Underlying disease
 Adequacy of compensatory responses
 Rate of bleeding
 Starting point